WO2005040087A1 - Method for the production of 6,6,6-trihalo-3,5-dioxohexanoic acid esters - Google Patents

Method for the production of 6,6,6-trihalo-3,5-dioxohexanoic acid esters Download PDF

Info

Publication number
WO2005040087A1
WO2005040087A1 PCT/EP2004/011970 EP2004011970W WO2005040087A1 WO 2005040087 A1 WO2005040087 A1 WO 2005040087A1 EP 2004011970 W EP2004011970 W EP 2004011970W WO 2005040087 A1 WO2005040087 A1 WO 2005040087A1
Authority
WO
WIPO (PCT)
Prior art keywords
formula
alkyl
cycloalkyl
enols
compound
Prior art date
Application number
PCT/EP2004/011970
Other languages
German (de)
French (fr)
Inventor
Paul Hanselmann
Wolfgang Wenger
Original Assignee
Lonza Ag
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Lonza Ag filed Critical Lonza Ag
Priority to CA002541843A priority Critical patent/CA2541843A1/en
Priority to EP04817266A priority patent/EP1680391A1/en
Priority to US10/577,070 priority patent/US7351851B2/en
Priority to JP2006536059A priority patent/JP4638441B2/en
Publication of WO2005040087A1 publication Critical patent/WO2005040087A1/en
Priority to US11/416,212 priority patent/US7348450B2/en
Priority to US12/071,991 priority patent/US7781601B2/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
    • C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
    • C07C69/738—Esters of keto-carboxylic acids or aldehydo-carboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/03—Preparation of carboxylic acid esters by reacting an ester group with a hydroxy group
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
    • C07D309/34—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D309/36—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms
    • C07D309/38—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms one oxygen atom in position 2 or 4, e.g. pyrones

Definitions

  • the invention relates to a ner process for the preparation of 6,6,6-trihalo-3,5-dioxohexanoic esters of the formula
  • substituents X are each independently fluorine, chlorine or bromine and 1 in which R is each alkyl, cycloalkyl, aryl or aralkyl, and R is alkyl, cycloalkyl, allyl or benzyl, starting from pyranones of the formula
  • Ethyl 6,6,6-trihalo-3,5-dioxohexanoate of the formula I are used, for example, for the preparation of herbicides and agrochemicals (JP-A-06-049039).
  • BEST ⁇ TIGU ⁇ GSKOPIE A ner process for the preparation of 6,6,6-trifluoro-3,5-dioxohexanoic acid tert-butyl ester from trifluoroacetic acid (2,2,2-trifluoroethyl) ester and acetoacetic acid tert-butyl ester is disclosed in OA-02/02547.
  • Another alternative production variant for substituted tricarbonyl compounds proceeds via the ring opening of a pyranone, such as, for example, dehydroacetic acid, which is converted into methyl 3,5-dioxohexanoic acid using Mg (OMe) 2 in methanol (Batelaan, JG, Synthetic Commun. 1976, 6, 81- 83).
  • a pyranone such as, for example, dehydroacetic acid
  • the object of the present invention was therefore to provide a simple ner process for the preparation of 6,6,6-trihalo-3,5-dioxohexanoic acid alkyl esters and their enols and enol ethers, which can use easily accessible pyrones as starting compounds.
  • the substituents X each independently represent fluorine, chlorine or bromine
  • the present process is characterized in that no mass loss occurs when the ring is opened and the number of carbon atoms contained in the basic structure is retained.
  • the starting compounds of formula II of the process according to the invention are easily accessible.
  • 4-hydroxy-6-trifluoromethyl-pyran-2-one can be prepared by reacting trifluoroacetic acid with ketene.
  • alkyl means in particular a linear or optionally branched group with 1 to 8 carbon atoms, optionally substituted with halogen, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl , Pentyl, hexyl, heptyl, octyl.
  • halogen such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl , Pentyl, hexyl, heptyl, octyl.
  • Cycloalkyl here and below means in particular a cyclic group with 3 to 8 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl.
  • aryl means in particular an aromatic group with 6 or 8 carbon atoms, optionally substituted with alkyl and or halogen, such as phenyl, p-to ⁇ y ⁇ or naphthyl.
  • aralkyl means in particular an alkyl group substituted by an aryl group, such as phenylethyl, where the alkyl group contains 1 to 4 carbon atoms, and the aryl group is an aromatic or heteroaromatic group optionally substituted by halogen, having 4 to 8 carbon atoms, such as for example phenyl, naphthyl, 2- or 3-furanyl, 2- or 3-thiophenyl or 2-, 3- or 4-pyridinyl.
  • aryl group such as phenylethyl
  • the alkyl group contains 1 to 4 carbon atoms
  • the aryl group is an aromatic or heteroaromatic group optionally substituted by halogen, having 4 to 8 carbon atoms, such as for example phenyl, naphthyl, 2- or 3-furanyl, 2- or 3-thiophenyl or 2-, 3- or 4-pyridinyl.
  • substituents X are each independently fluorine, chlorine or bromine and in which R 1 is each alkyl, cycloalkyl, aryl or aralkyl, and R 2 is alkyl, cycloalkyl, allyl or benzyl, compounds of the formula
  • Suitable reagents for the preparation of compounds of the formula III according to the invention are, for example, dimethyl sulfate, diethyl sulfate, methyl iodide, ethyl bromide, methyl tosylate, ethyl tosylate, phenyl tosylate, allyl chloride, allyl bromide, benzyl chloride or benzyl bromide.
  • O ⁇ ⁇ M n + means M n + preferably Li + , Na + , K + ,
  • strong acids are understood to mean, for example, HCl, HBr, HI, H 2 SO, trifluoroacetic acid or solid acids such as, for example, acidic zeolites such as H-ZSM-5 or acidic sheet silicates.
  • Weak acids in the process according to the invention are understood to mean, for example, acetic acid and aqueous dilute acids of HCl, H3PO 4 or H 3 SO 4 or the addition of strong acids after adding water beforehand.
  • compounds of the formula III are converted into compounds of the formula I in which X is fluorine and R 1 -s-alkyl, the radical R 2 being split off.
  • R 1 is C 1-4 alkyl.
  • R 1 is methyl.
  • Z isomers is influenced by various influences such as, for example, the solvent, the temperature or, if appropriate, by protonating or deprotonating additives.
  • the solvent the temperature or, if appropriate, by protonating or deprotonating additives.
  • the enols of compounds of the formula I differ from one another by the enolized carbonyl group and the position and orientation of the resulting double bond (s).
  • the carbonyl groups at C 3 and / or C 5 can be enolized.
  • the enols are usually in the form of mixtures of several forms.
  • the invention also includes compounds of the formula
  • X each independently represents F, Cl or Br and wherein R 2 is alkyl, cycloalkyl, allyl or benzyl.
  • E and Z isomers in which X each independently denotes F, Cl or Br, and in which R 1 is alkyl, cycloalkyl, aryl or aralkyl, and in which R 2 is alkyl, cycloalkyl, allyl or benzyl.
  • the compounds of the formula Ib can be present as E and / or Z isomers. Depending on the external conditions, only the carbonyl group at C 5 can be enolized. The number and position of the resulting double bonds at C 2 / C 3 and / or C 4 / C 5 correspond to the E and Z isomers of the oleols of the compounds of the formula I.
  • 3,3,3-Trihalo-3,5-dioxohexanoic acid alkyl esters can be prepared from 4-methoxy-6-trihalomethyl-pyran-2-ones by the process described above.
  • 6,6,6-trifluoro-3,5-dioxohexanoic acid methyl ester is prepared from 4-methoxy-6-trifluoromethyl-pyran-2-one.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pyrane Compounds (AREA)

Abstract

The invention relates to a method for the production of 6,6,6-trihalo-3,5-dioxohexanic acid esters of formula (I) in addition to the enols thereof and E and Z isomers, wherein X independently represents fluorine, chlorine or bromine and R<1> represents alkyl, cycloalkyl, aryl or aralkyl. The invention also relates to a method for the production of enol ethers of formula (Ib) and the enols thereof (E and Z isomers) wherein X and R<1> have the above-mentioned meaning.

Description

Verfahren zur Herstellung von 6,6,6-TrihaIo-3,5-dioxohexansäureesternProcess for the preparation of 6,6,6-trihao-3,5-dioxohexanoic acid esters
Die Erfindung betrifft ein Nerfahren zur Herstellung von 6,6,6-Trihalo-3,5-dioxohexansäure- estern der FormelThe invention relates to a ner process for the preparation of 6,6,6-trihalo-3,5-dioxohexanoic esters of the formula
Figure imgf000002_0001
sowie deren Enolen und E- und Z-Isomeren oder deren Enolethern der Formel
Figure imgf000002_0001
and their enols and E and Z isomers or their enol ethers of the formula
Figure imgf000002_0002
sowie deren Enolen und E- und Z-Isomeren worin die Substituenten X jeweils unabhängig voneinander Fluor, Chlor oder Brom sind und 1 worin R jeweils Alkyl, Cycloalkyl, Aryl oder Aralkyl, sowie R Alkyl, Cycloalkyl, Allyl oder Benzyl bedeuten, ausgehend von Pyranonen der Formel
Figure imgf000002_0002
and their enols and E and Z isomers in which the substituents X are each independently fluorine, chlorine or bromine and 1 in which R is each alkyl, cycloalkyl, aryl or aralkyl, and R is alkyl, cycloalkyl, allyl or benzyl, starting from pyranones of the formula
Figure imgf000002_0003
worin X die oben genannte Bedeutung hat.
Figure imgf000002_0003
where X has the meaning given above.
6,6,6-Trihalo-3,5-dioxohexansäureethylester der Formel I werden beispielsweise zur Herstellung von Herbiziden und Agrochemikalien (JP-A-06-049039) eingesetzt.Ethyl 6,6,6-trihalo-3,5-dioxohexanoate of the formula I are used, for example, for the preparation of herbicides and agrochemicals (JP-A-06-049039).
Bekannte Verfahren zur Synthese von substituierten Tricarbonylverbindungen mit einer 3,5-Dioxohexansäureester-Grundstruktur gehen beispielsweise von Acetessigsäureethylester aus, der in THF mit Benzoesäureethylester in Gegenwart von KH/BuLi (WO-A-94/11361), oder in THF mit einem hochsubstituierten 3-Oxopentansäureamid in Gegenwart von ΝaH/BuLi (WO-A-02/055519) kondensiert wird.Known processes for the synthesis of substituted tricarbonyl compounds with a 3,5-dioxohexanoic acid ester structure are based, for example, on ethyl acetoacetate, which in THF with ethyl benzoate in the presence of KH / BuLi (WO-A-94/11361), or in THF with a highly substituted 3 -Oxopentanoic acid amide is condensed in the presence of ΝaH / BuLi (WO-A-02/055519).
BESTÄTIGUΝGSKOPIE Ein Nerfahren zur Herstellung von 6,6,6-Trifluor-3,5-dioxohexansäure-tert-butylester aus Trifluoressigsäure-(2,2,2-trifluorethyl)ester und Acetessigsäure-tert-butylester ist in O-A-02/02547 offenbart.BESTÄTIGUΝGSKOPIE A ner process for the preparation of 6,6,6-trifluoro-3,5-dioxohexanoic acid tert-butyl ester from trifluoroacetic acid (2,2,2-trifluoroethyl) ester and acetoacetic acid tert-butyl ester is disclosed in OA-02/02547.
Eine weitere alternative Herstellungsvariante für substituierte Tricarbonylverbindungen verläuft über die Ringöffnung eines Pyranons, wie beispielsweise der Dehydracetsäure, die mittels Mg(OMe)2 in Methanol in 3,5-Dioxohexansäuremethylester übergeführt wird (Batelaan, J.G., Synthetic Commun. 1976, 6, 81-83).Another alternative production variant for substituted tricarbonyl compounds proceeds via the ring opening of a pyranone, such as, for example, dehydroacetic acid, which is converted into methyl 3,5-dioxohexanoic acid using Mg (OMe) 2 in methanol (Batelaan, JG, Synthetic Commun. 1976, 6, 81- 83).
Diese bekannten Methoden haben den Nachteil, dass kostspielige Reagentien wie BuLi verwendet werden.These known methods have the disadvantage that expensive reagents such as BuLi are used.
Aus Solladie, et al., Tetrahedron: Asymmetry 1996, 7, 2371-2379 ist bekannt, dass die Ringöff ung von Dehydracetsäure der FormelFrom Solladie, et al., Tetrahedron: Asymmetry 1996, 7, 2371-2379 it is known that the ring opening of dehydroacetic acid of the formula
Figure imgf000003_0001
zur Tricarbonylverbindung möglich ist, jedoch zur Abspaltung des Acetyl-Substituenten fuhrt, der zuvor während der Synthese eingeführt wurde. Ein Masseverlust wirkt sich jedoch bei industrieller Prozessführung nachteilig auf die Rentabilität eines Nerfahrens aus.
Figure imgf000003_0001
is possible to the tricarbonyl compound, but leads to the cleavage of the acetyl substituent that was previously introduced during the synthesis. In industrial process control, however, a loss of mass adversely affects the profitability of a ner driving.
Aufgabe der vorliegenden Erfindung war daher die Bereitstellung eines einfachen Nerfahrens zur Herstellung von 6,6,6-Trihalo-3,5-dioxohexansäurealkylestern sowie deren Enolen und Enolethern, das leicht zugängliche Pyrone als Ausgangsverbindungen nutzen kann.The object of the present invention was therefore to provide a simple ner process for the preparation of 6,6,6-trihalo-3,5-dioxohexanoic acid alkyl esters and their enols and enol ethers, which can use easily accessible pyrones as starting compounds.
Erfindungsgemäss wird diese Aufgabe durch das Verfahren gemäss Patentanspruch 1 gelöst.According to the invention, this object is achieved by the method according to claim 1.
Es wurde gefunden, dass Verbindungen der FormelIt has been found that compounds of the formula
Figure imgf000003_0002
worin die Substituenten X jeweils unabhängig voneinander Fluor, Chlor oder Brom bedeuten, nach Umsetzung der Hydroxygruppe in eine Ethergruppe und nachfolgender Öffnung des Pyranringes mit einem Metallalkoholat abhängig von den weiteren Reaktionsbedingungen Verbindungen der Formel I oder deren Enolether der Formel Ib in guter Ausbeute liefern. Das vorliegende Verfahren zeichnet sich dadurch aus, dass bei der Ringöffnung kein Massenverlust entsteht und die Zahl der im Grundgerüst enthaltenen Kohlenstoffatome erhalten bleibt.
Figure imgf000003_0002
in which the substituents X each independently represent fluorine, chlorine or bromine, after reaction of the hydroxyl group in an ether group and subsequent opening of the pyran ring with a metal alcoholate, depending on the further reaction conditions, provide compounds of the formula I or their enol ethers of the formula Ib in good yield. The present process is characterized in that no mass loss occurs when the ring is opened and the number of carbon atoms contained in the basic structure is retained.
Das erfindungsgemässe Verfahren ist überraschend, da bekannt ist, dass sich 4-Hydroxy- pyran-2-on durch Umsetzung mit Natriummethanolat nicht in die offenkettige Tricarbonylverbindung überführen lässt, sondern gemäss untenstehender Reaktionsgleichung, zuerst an der Hydroxygruppe methyliert und anschliessend der Pyranonether in ein Phloroglucinderivat übergeführt wird (Effenberger, F. et al., Chem. Ber. 1984, 117, 3270-3279).The process according to the invention is surprising since it is known that 4-hydroxy-pyran-2-one cannot be converted into the open-chain tricarbonyl compound by reaction with sodium methoxide, but rather, according to the reaction equation below, first methylated on the hydroxyl group and then the pyranone ether is converted into a phloroglucin derivative is transferred (Effenberger, F. et al., Chem. Ber. 1984, 117, 3270-3279).
Figure imgf000004_0001
Figure imgf000004_0001
Die sich im erfindungsgemässen Verfahren ergebende Ringöff ung konnte somit nicht erwartet werden.The ring opening resulting in the process according to the invention could therefore not be expected.
Die Ausgangsverbindungen der Formel II des erfindungsgemässen Verfahrens sind leicht zugänglich. So lässt sich beispielsweise 4-Hydroxy-6-trifluormethyl-pyran-2-on durch Umsetzen von Trifluoressigsäure mit Keten herstellen.The starting compounds of formula II of the process according to the invention are easily accessible. For example, 4-hydroxy-6-trifluoromethyl-pyran-2-one can be prepared by reacting trifluoroacetic acid with ketene.
Unter Alkyl wird hier und im Folgenden insbesondere eine, gegebenenfalls mit Halogen substituierte, lineare oder gegebenenfalls verzweigte Gruppe mit 1 bis 8 Kohlenstoffatomen verstanden, wie beispielsweise Methyl, Ethyl, Propyl, Isopropyl, «-Butyl, Isobutyl, sec-Butyl, tert-Butyl, Pentyl, Hexyl, Heptyl, Octyl.Here and below, alkyl means in particular a linear or optionally branched group with 1 to 8 carbon atoms, optionally substituted with halogen, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl , Pentyl, hexyl, heptyl, octyl.
Unter Cycloalkyl wird hier und im Folgenden insbesondere eine cylische Gruppe mit 3 bis 8 Kohlenstoffatomen verstanden, wie beispielsweise Cyclopropyl, Cyclobutyl, Cyclopentyl, Cyclohexyl, Cycloheptyl, Cyclooctyl. Unter Aryl wird hier und im Folgenden insbesondere eine, gegebenenfalls mit Alkyl und oder Halogen substituierte, aromatische Gruppe mit 6 oder 8 Kohlenstoffatomen verstanden, wie beispielsweise Phenyl, p-To\y\ oder Naphthyl.Cycloalkyl here and below means in particular a cyclic group with 3 to 8 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl. Here and below, aryl means in particular an aromatic group with 6 or 8 carbon atoms, optionally substituted with alkyl and or halogen, such as phenyl, p-to \ y \ or naphthyl.
Unter Aralkyl wird hier und im Folgenden insbesondere eine mit einer Arylgruppe substituierte Alkylgruppe wie beispielsweise Phenylethyl verstanden, wobei die Alkylgruppe 1 bis 4 Kohlenstoffatomen enthält, und die Arylgruppe eine, gegebenenfalls mit Halogen substituierte, aromatische oder heteroaromatische Gruppe mit 4 bis 8 Kohlenstoffatomen ist, wie beispielsweise Phenyl, Naphthyl, 2- oder 3-Furanyl, 2- oder 3-Thiophenyl oder 2-, 3- oder 4-Pyridinyl.Here and below, aralkyl means in particular an alkyl group substituted by an aryl group, such as phenylethyl, where the alkyl group contains 1 to 4 carbon atoms, and the aryl group is an aromatic or heteroaromatic group optionally substituted by halogen, having 4 to 8 carbon atoms, such as for example phenyl, naphthyl, 2- or 3-furanyl, 2- or 3-thiophenyl or 2-, 3- or 4-pyridinyl.
In dem erfindungsgemässen Verfahren zur Herstellung von Verbindungen der FormelIn the process according to the invention for the preparation of compounds of the formula
Figure imgf000005_0001
sowie deren Enolen und E- und Z-Isomeren oder deren Enolethern der Formel
Figure imgf000005_0001
and their enols and E and Z isomers or their enol ethers of the formula
Figure imgf000005_0002
sowie deren Enolen und E- und Z-Isomeren worin die Substituenten X jeweils unabhängig voneinander Fluor, Chlor oder Brom sind und worin R1 jeweils Alkyl, Cycloalkyl, Aryl oder Aralkyl, sowie R2 Alkyl, Cycloalkyl, Allyl oder Benzyl bedeuten, werden Verbindungen der Formel
Figure imgf000005_0002
and their enols and E and Z isomers in which the substituents X are each independently fluorine, chlorine or bromine and in which R 1 is each alkyl, cycloalkyl, aryl or aralkyl, and R 2 is alkyl, cycloalkyl, allyl or benzyl, compounds of the formula
Figure imgf000005_0003
worin X vorstehend genannte Bedeutung hat, durch Reaktion der Hydroxygruppe mit einer Verbindung der Formel (R2O)2SO2 oder einer Verbindung der Formel Y-R2, worin Y Tosyl, Chlor, Brom oder Iod bedeutet und worin R2 jeweils die oben genannte Bedeutung hat, in eine Verbindung der Formel
Figure imgf000005_0003
wherein X has the meaning given above, by reaction of the hydroxyl group with a compound of the formula (R 2 O) 2 SO 2 or a compound of the formula YR 2 , in which Y is tosyl, Chlorine, bromine or iodine and in which R 2 each has the meaning given above, into a compound of the formula
Figure imgf000006_0001
worin R2 und X die genannten Bedeutungen haben, übergeführt und der Pyranonring des Reaktionsproduktes anschliessend durch Umsetzung mit einem Metallalkoholat der Formel R1^ Mn+, worin R1 die oben genannte Bedeutung hat und Mn+ ein Alkali- oder Erdalkalimetallkation und n=l oder 2 bedeutet, abhängig von den weiteren Umsetzungsbedingungen zu Verbindungen der Formel I oder Ib geöffnet wird.
Figure imgf000006_0001
wherein R 2 and X have the meanings mentioned, and the pyranone ring of the reaction product is then converted by reaction with a metal alcoholate of the formula R 1 ^ M n + , wherein R 1 has the meaning given above and M n + is an alkali metal or alkaline earth metal cation and n = l or 2 means, depending on the further reaction conditions to give compounds of the formula I or Ib.
Geeignete Reagenzien für die erfϊndungsgemässe Herstellung von Verbindungen der Formel III sind beispielsweise Dimethylsulfat, Diethylsulfat, Methyliodid, Ethylbromid, Methyltosylat, Ethyltosylat, Phenyltosylat, Allylchlorid, Allylbromid, Benzylchlorid oder Benzylbromid.Suitable reagents for the preparation of compounds of the formula III according to the invention are, for example, dimethyl sulfate, diethyl sulfate, methyl iodide, ethyl bromide, methyl tosylate, ethyl tosylate, phenyl tosylate, allyl chloride, allyl bromide, benzyl chloride or benzyl bromide.
In den Metallalkoholaten der Formel R!O~ ^Mn+ bedeutet Mn+ vorzugsweise Li+, Na+, K+,In the metal alcoholates of the formula R ! O ~ ^ M n + means M n + preferably Li + , Na + , K + ,
Mg2+ oder Ca2+.Mg 2+ or Ca 2+ .
Wenn dem Reaktionsgemisch aus Verbindungen der Formel III nach erfolgter Zugabe des Metallalkoholats eine starke Säure zugesetzt (pH <1) und das Gemisch weiter umgesetzt wird, sind Verbindungen der Formel I und deren Enole erhältlich. Bei diesem Verfahren wird der Rest R abgespalten. Wenn dem Reaktionsgemisch aus Verbindungen der Formel III nach erfolgter Zugabe des Metallalkoholats eine schwache oder gar keine Säure zugesetzt und das Gemisch weiter umgesetzt wird, sind Enolether der Formel Ib und deren Enole erhältlich. Bei dieser Verfahrensvariante bleibt der Rest R2 erhalten. Die Enolether der Formel Ib lassen sich nach Zusatz starker Säuren und unter stark sauren Bedingungen unter Abspaltung des Restes R2 in schlechten Ausbeuten ebenfalls in Verbindungen der Formel I und deren Enole überführen. Unter starken Säuren werden im erfindungsgemässen Verfahren beispielsweise HCl, HBr, HI, H2SO , Trifluoressigsäure oder Festkörpersäuren wie beispielsweise saure Zeolithe wie H-ZSM-5 oder saure Schichtsilikate verstanden.If a strong acid (pH <1) is added to the reaction mixture of compounds of the formula III after the metal alcoholate has been added and the mixture is reacted further, compounds of the formula I and their enols are obtainable. In this process, the remainder R is split off. If a weak or no acid is added to the reaction mixture of compounds of the formula III after the metal alcoholate has been added and the mixture is reacted further, enol ethers of the formula Ib and their enols are obtainable. In this process variant, the R 2 radical is retained. The enol ethers of the formula Ib can also be converted into compounds of the formula I and their enols after addition of strong acids and under strongly acidic conditions with elimination of the radical R 2 in poor yields. In the process according to the invention, strong acids are understood to mean, for example, HCl, HBr, HI, H 2 SO, trifluoroacetic acid or solid acids such as, for example, acidic zeolites such as H-ZSM-5 or acidic sheet silicates.
Unter schwachen Säuren werden im erfindungsgemässen Verfahren beispielsweise Essigsäure und wässerige verdünnte Säuren von HCl, H3PO4 oder H3SO4 oder die Zugabe von starken Säuren nach vorheriger Zugabe von Wasser verstanden.Weak acids in the process according to the invention are understood to mean, for example, acetic acid and aqueous dilute acids of HCl, H3PO 4 or H 3 SO 4 or the addition of strong acids after adding water beforehand.
In einer bevorzugten Ausführungsform werden Verbindungen der Formel III in Verbindungen der Formel I übergeführt, worin X Fluor und R1 -s-Alkyl bedeutet, wobei der Rest R2 abgespalten wird. In einer weiteren bevorzugten Ausführungsform bedeutet R1 C1-4-Alkyl. In einer besonders bevorzugten Ausführungsforrn ist R1 Methyl.In a preferred embodiment, compounds of the formula III are converted into compounds of the formula I in which X is fluorine and R 1 -s-alkyl, the radical R 2 being split off. In a further preferred embodiment, R 1 is C 1-4 alkyl. In a particularly preferred embodiment, R 1 is methyl.
Als Verbindungen der Formel I werden im erfindungsgemässen Verfahren auch die entsprechenden Enole wie beispielsweise der FormelnThe corresponding enols such as, for example, the formulas are also used as compounds of the formula I in the process according to the invention
Figure imgf000007_0001
(E- und Z-Isomere) oder
Figure imgf000007_0001
(E and Z isomers) or
Figure imgf000007_0002
(E- und Z-Isomere) einzeln oder als Gemisch verstanden und sind durch die Erfindung mit umfasst. Die Gleich- gewichtsverteilung von Verbindungen der Formel Ia zu ihren Enolformen (als E- und
Figure imgf000007_0002
(E and Z isomers) understood individually or as a mixture and are also encompassed by the invention. The equilibrium distribution of compounds of the formula Ia to their enol forms (as E and
Z-Isomere), wird durch verschiedene Einflüsse wie beispielsweise das Lösungsmittel, die Temperatur oder gegebenenfalls durch protonierende oder deprotonierende Zusätze beeinflusst. Nach Kugelrohrdestillation liegt beispielsweise Verbindung Ia mit X = Fluor und R1 = Methyl ohne Lösungsmittel bei Raumtemperatur überwiegend als Monoenol der Formel Ia' vor.Z isomers), is influenced by various influences such as, for example, the solvent, the temperature or, if appropriate, by protonating or deprotonating additives. After Kugelrohr distillation, for example, compound Ia with X = fluorine and R 1 = methyl without solvent is present predominantly as a monoenol of the formula Ia 'at room temperature.
Die Enole von Verbindungen der Formel I unterscheiden sich untereinander durch die enolisierte Carbonylgruppe und die Lage und Orientierung der entstehenden Doppel- bindung(en). Enolisiert werden können die Carbonylgruppen an C3 und/oder C5. Es können dabei jeweils eine Doppelbindung zwischen den Kohlenstoffatomen C2/C3, C3/C4, C /C5 oder konjugierte Doppelbindungen zwischen C2/C3 und C4/C5 vorliegen, wobei die Doppelbindungen ausserdem in E- oder Z-Konfiguration vorliegen können. Die Enole liegen meist als Gemische mehrerer Formen vor.The enols of compounds of the formula I differ from one another by the enolized carbonyl group and the position and orientation of the resulting double bond (s). The carbonyl groups at C 3 and / or C 5 can be enolized. There can be a double bond between the carbon atoms C 2 / C 3 , C 3 / C 4 , C / C 5 or conjugated double bonds between C 2 / C 3 and C 4 / C 5 , the double bonds also in E or Z configuration may exist. The enols are usually in the form of mixtures of several forms.
Von der Erfindung mit umfasst sind ebenfalls Verbindungen der FormelThe invention also includes compounds of the formula
Figure imgf000008_0001
worin X jeweils unabhängig voneinander F, Cl oder Br bedeutet und worin R2 Alkyl, Cycloalkyl, Allyl oder Benzyl ist.
Figure imgf000008_0001
wherein X each independently represents F, Cl or Br and wherein R 2 is alkyl, cycloalkyl, allyl or benzyl.
Ebenfalls mit von der Erfindung umfasst sind Enolether der FormelAlso included in the invention are enol ethers of the formula
Figure imgf000008_0002
(E- und Z-Isomere) und deren Enolen wie beispielsweise
Figure imgf000008_0002
(E and Z isomers) and their enols such as
Figure imgf000008_0003
(E- und Z-Isomere) worin X jeweils unabhängig voneinander F, Cl oder Br bedeutet, und worin R1 Alkyl, Cycloalkyl, Aryl oder Aralkyl ist, sowie worin R2 Alkyl, Cycloalkyl, Allyl oder Benzyl ist. Die Verbindungen der Formel Ib können, ebenso wie die vorstehend beschriebenen Verbindungen der Formel I, als E- und/oder Z-Isomere vorliegen. Abhängig von den äusseren Bedingungen kann allerdings nur noch die Carbonylgruppe an C5 enolisiert werden. Anzahl und Lage der resultierenden Doppelbindungen an C2/C3 und-/oder C4/C5 entsprechen den E- und Z-Isomeren der Εnole der Verbindungen der Formel I. 3,3,3-Trihalo-3,5-dioxohexansäurealkylester können nach oben beschriebenem Verfahren aus 4-Methoxy-6-trihalomethyl-pyran-2-onen hergestellt werden. Vorzugsweise wird 6,6,6-Trifluor-3 ,5 -dioxohexansäuremethylester aus 4-Methoxy-6-trifluormethyl-pyran-2-on hergestellt.
Figure imgf000008_0003
(E and Z isomers) in which X each independently denotes F, Cl or Br, and in which R 1 is alkyl, cycloalkyl, aryl or aralkyl, and in which R 2 is alkyl, cycloalkyl, allyl or benzyl. The compounds of the formula Ib, like the compounds of the formula I described above, can be present as E and / or Z isomers. Depending on the external conditions, only the carbonyl group at C 5 can be enolized. The number and position of the resulting double bonds at C 2 / C 3 and / or C 4 / C 5 correspond to the E and Z isomers of the oleols of the compounds of the formula I. 3,3,3-Trihalo-3,5-dioxohexanoic acid alkyl esters can be prepared from 4-methoxy-6-trihalomethyl-pyran-2-ones by the process described above. Preferably 6,6,6-trifluoro-3,5-dioxohexanoic acid methyl ester is prepared from 4-methoxy-6-trifluoromethyl-pyran-2-one.
BeispieleExamples
Die folgenden Beispiele verdeutlichen die Durchführung des erfindungsgemässen Verfahrens, ohne dass darin eine Einschränkung zu sehen ist.The following examples illustrate the implementation of the method according to the invention, without any limitation being seen therein.
Beispiel 1example 1
4-Methoxy-6-trifluormethyl-pyran-2-on (III; R2 = Methyl, X = Fluor)4-methoxy-6-trifluoromethyl-pyran-2-one (III; R 2 = methyl, X = fluorine)
Zu einer Lösung von 4-Hydroxy-6-trifluormethyl-pyran-2-on (3,0 g, 17 mmol) in AcetonTo a solution of 4-hydroxy-6-trifluoromethyl-pyran-2-one (3.0 g, 17 mmol) in acetone
(50 mL) wurden Natriumcarbonat (1,35 g, 13 mmol) und Dimethylsulfat (2,17 g, 17 mmol) gegeben. Die Mischung wurde während 3 Stunden unter Rückfluss erhitzt und nach dem(50 mL) sodium carbonate (1.35 g, 13 mmol) and dimethyl sulfate (2.17 g, 17 mmol) were added. The mixture was heated under reflux for 3 hours and after that
Abkühlen filtriert. Nach dem Einengen des Filtrats wurden 2,9 g rohes Produkt als braunes Öl erhalten. Durch Kristallisation aus Hexan konnte 4-Methoxy-6-trifluormethyl-pyran-2-on (2,74 g, 14 mmol, 83%) als farblose Nadeln mit einem Schmelzpunkt von 61 °C erhalten werden. 1H NMR (400 MHz, OMSO-d6) δ: 7,01 (d, J= 1,6 Hz, 1H), 5,98 (d, J= 1,6 Hz, 1H), 3,7 (s, 3H).Cool filtered. After concentrating the filtrate, 2.9 g of crude product were obtained as a brown oil. Crystallization from hexane gave 4-methoxy-6-trifluoromethyl-pyran-2-one (2.74 g, 14 mmol, 83%) as colorless needles with a melting point of 61 ° C. 1H NMR (400 MHz, OMSO-d 6 ) δ: 7.01 (d, J = 1.6 Hz, 1H), 5.98 (d, J = 1.6 Hz, 1H), 3.7 (s , 3H).
Beispiel 2Example 2
6,6,6-Trifiuor-2-methoxy-5-oxo-2-hexensäuremethylester (Ib; R1 = R2 = Methyl, X = Fluor)6,6,6-trifiuor-2-methoxy-5-oxo-2-hexenoic acid methyl ester (Ib; R 1 = R 2 = methyl, X = fluorine)
Figure imgf000009_0001
sowie deren Enole und E- und Z-Isomere
Figure imgf000009_0001
and their enols and E and Z isomers
Eine Lösung von 4-Methoxy-6-trifluormethyl-pyran-2-on (2,7 g, 14 mmol) in einer methanolischen Magnesiummethanolatlösung (8,5% Mg(OMe)2, 8,36 g, 8 mmol) wurde während 16 Stunden unter Rückfluss erhitzt. Die Lösung wurde eingeengt, in Wasser und Ethylacetat aufgenommen und die organische Phase durch Zugabe von verdünnter Salzsäure auf pH 5 gebracht. Die organische Phase wurde abgetrennt, getrocknet und eingeengt. Es wurde 1,5 g rohes Produkt als gelbes Öl erhalten. Kugelrohrdestillation bei 0,04 mbar und ca. 160 °C ergab 6,6,6-Trifluor-3-methoxy-5-oxo-2-hexensäuremethylester (1,50 g, 6,6 mmol, 48%) als leicht gelbes Öl. Daten der Hauptverbindung: !H NMR (400 MHz, DMSO-t 6 δ (Resonanzlinien der Enolform Ib, ohne E/Z-Bestimmung): 6,05 (s, 1H), 3,9 (s, 3H), 3,82 (s, 2H), 3,62 (s, 3H). 19F-NMR (386 MHz, OMSO-d6) δ: -76,8. MS: 227 [M+H]+.A solution of 4-methoxy-6-trifluoromethyl-pyran-2-one (2.7 g, 14 mmol) in a methanolic magnesium methoxide solution (8.5% Mg (OMe) 2 , 8.36 g, 8 mmol) was added during Heated under reflux for 16 hours. The solution was concentrated, taken up in water and ethyl acetate and the organic phase was brought to pH 5 by adding dilute hydrochloric acid. The organic phase was separated, dried and concentrated. It 1.5 g of crude product was obtained as a yellow oil. Kugelrohr distillation at 0.04 mbar and approx. 160 ° C. gave 6,6,6-trifluoro-3-methoxy-5-oxo-2-hexenoic acid methyl ester (1.50 g, 6.6 mmol, 48%) as a slightly yellow oil , Main connection data :! H NMR (400 MHz, DMSO-t 6 δ (resonance lines of enol form Ib, without E / Z determination): 6.05 (s, 1H), 3.9 (s, 3H), 3.82 (s, 2H ), 3.62 (s, 3H). 19 F-NMR (386 MHz, OMSO-d 6 ) δ: -76.8. MS: 227 [M + H] + .
Beispiel 3Example 3
6,6,6-Trifluor-3,5-dioxohexansäuremethylester (I; R1 = Methyl, X = Fluor)6,6,6-trifluoro-3,5-dioxohexanoic acid methyl ester (I; R 1 = methyl, X = fluorine)
Figure imgf000010_0001
sowie deren Εnole und E- und Z-Isomere
Figure imgf000010_0001
as well as their oleols and E and Z isomers
Eine Lösung von 4-Methoxy-6-trifluormethyl-pyran-2-on (10 g, 52 mmol) in einer methanolischen Magnesiummethanolatlösung (8,5% Mg(OMe)2, 62,8 g, 61 mmol) wurde während 2 Stunden unter Rückfluss erhitzt. Die Reaktionslösung wurde mit konzentrierter wässriger HCl (25,5 g, 250 mmol) versetzt und weitere 2 Stunden unter Rückfluss erhitzt, anschliessend abgekühlt und unter Vakuum auf ca. 20% des Ausgangsvolumens eingeengt. Der Rückstand wurde mit jeweils 10 mL Methylenchlorid und Wasser versetzt. Die organische Phase wurde abgetrennt, mit Wasser gewaschen, über Natriumsulfat getrocknet und eingeengt. Kugelrohrdestillation bei 0,04 mbar und ca. 160 °C ergab 6,6,6-Trifluor-3,5- dioxohexansäuremethylester (2,8 g, 13 mmol, 26%) als leicht gelbes Öl. Daten der Hauptverbindung:A solution of 4-methoxy-6-trifluoromethyl-pyran-2-one (10 g, 52 mmol) in a methanolic magnesium methoxide solution (8.5% Mg (OMe) 2 , 62.8 g, 61 mmol) was added over 2 hours heated under reflux. Concentrated aqueous HCl (25.5 g, 250 mmol) was added to the reaction solution and the mixture was heated under reflux for a further 2 hours, then cooled and concentrated to about 20% of the starting volume in vacuo. The residue was mixed with 10 mL methylene chloride and water. The organic phase was separated, washed with water, dried over sodium sulfate and concentrated. Kugelrohr distillation at 0.04 mbar and approx. 160 ° C gave methyl 6,6,6-trifluoro-3,5-dioxohexanoate (2.8 g, 13 mmol, 26%) as a slightly yellow oil. Main connection data:
1H NMR (400 MHz, OMSO-d6) δ (Resonanzlinien der Enolform Ia', ohne E/Z-Bestimmung): 6,0 (br, 2H), 3,8 (s, 2H), 3,65 (s, 3H).1H NMR (400 MHz, OMSO-d 6 ) δ (resonance lines of enol form Ia ', without E / Z determination): 6.0 (br, 2H), 3.8 (s, 2H), 3.65 (s , 3H).
13C-NMR (100 MHz, OMSO-d6) δ (Resonanzlinien der Enolform Ia', ohne E/Z-Bestimmung): 181,6 (s), 167,7 (s), 116,9 (q, C-F 286 Hz), 95,9 (t), 52,0 (q), 49,7 (t), C-3 nicht erkennbar. MS: 212 (M+). 13 C-NMR (100 MHz, OMSO-d 6 ) δ (resonance lines of enol form Ia ', without E / Z determination): 181.6 (s), 167.7 (s), 116.9 (q, C - F 286 Hz), 95.9 (t), 52.0 (q), 49.7 (t), C-3 not recognizable. MS: 212 (M + ).

Claims

Ansprüche: Expectations:
1. Verfahren zur Herstellung von Verbindungen der Formel1. Process for the preparation of compounds of the formula
Figure imgf000011_0001
sowie deren Enolen und E- und Z-Isomeren worin X jeweils unabhängig voneinander Fluor, Chlor oder Brom bedeutet und worin R1 Alkyl, Cycloalkyl, Aryl oder Aralkyl ist, dadurch gekennzeichnet, dass eine Verbindung der Formel
Figure imgf000011_0001
and their enols and E and Z isomers in which X is independently fluorine, chlorine or bromine and in which R 1 is alkyl, cycloalkyl, aryl or aralkyl, characterized in that a compound of the formula
Figure imgf000011_0002
worin X die genannte Bedeutung hat, zunächst durch Reaktion der Hydroxygruppe mit einer Verbindung der Formel (R O) SO oder einer Verbindung der Formel Y-R , wor Y Tosyl, Chlor, Brom oder Iod bedeutet und worin R2 jeweils die oben genannte Bedeutung hat in eine Verbindung der Formel
Figure imgf000011_0002
in which X has the meaning given, first by reaction of the hydroxyl group with a compound of the formula (RO) SO or a compound of the formula YR, where Y is tosyl, chlorine, bromine or iodine and where R 2 in each case has the meaning given above in one Compound of formula
Figure imgf000011_0003
worin R Alkyl, Cycloalkyl, Allyl oder Benzyl ist und X die genannte Bedeutung hat, übergeführt wird, und diese anschliessend durch Umsetzung mit einem Metallalkoholat der Formel lO~ Mn+, worin R1 Alkyl, Cycloalkyl, Aryl oder Aralkyl und Mn+ ein Alkali- oder Erdalkalimetallkation und n = 1 oder 2 bedeutet, und weitere Behandlung mit einer starken Säure zu Verbindungen der Formel I und/oder deren Enole umgesetzt wird. Verfahren zur Herstellung von Enolethern der Formel
Figure imgf000011_0003
wherein R is alkyl, cycloalkyl, allyl or benzyl and X has the meaning given, and this is subsequently converted by reaction with a metal alcoholate of the formula I O ~ M n + , wherein R 1 is alkyl, cycloalkyl, aryl or aralkyl and M n + Alkali or alkaline earth metal cation and n = 1 or 2 means, and further treatment with a strong acid to give compounds of formula I and / or their enols. Process for the preparation of enol ethers of the formula
Figure imgf000012_0001
sowie deren Enolen und E- und Z-Isomeren worin X jeweils unabhängig voneinander F, Cl oder Br und worin R1 Alkyl, Cycloalkyl, Aryl oder Aralkyl, sowie R2 Alkyl, Cycloalkyl, Allyl oder Benzyl ist, dadurch gekennzeichnet, dass eine Verbindung der Formel
Figure imgf000012_0001
as well as their enols and E and Z isomers in which X is independently F, Cl or Br and in which R 1 is alkyl, cycloalkyl, aryl or aralkyl, and R 2 is alkyl, cycloalkyl, allyl or benzyl, characterized in that a compound of the formula
Figure imgf000012_0002
worin X die genannte Bedeutung hat, zunächst durch Reaktion der Hydroxygruppe mit einer Verbindung der Formel (R2O)2SO2 oder einer Verbindung der Formel Y-R2, worin Y Tosyl, Chlor, Brom oder Iod bedeutet und worin R jeweils die oben genannte Bedeutung hat in eine Verbindung der Formel
Figure imgf000012_0002
wherein X has the meaning given, first by reaction of the hydroxyl group with a compound of the formula (R 2 O) 2 SO 2 or a compound of the formula YR 2 , in which Y is tosyl, chlorine, bromine or iodine and in which R in each case the above Meaning in a compound of the formula
Figure imgf000012_0003
Figure imgf000012_0003
worin R2 Alkyl, Cycloalkyl, Allyl oder Benzyl ist und X die genannte Bedeutung hat, übergeführt wird, und diese anschliessend durch Umsetzung mit einem Metallalkoholat der Formel R1©" ^Mn+, worin R1 Alkyl, Cycloalkyl, Aryl oder Aralkyl und und Mn+ einin which R 2 is alkyl, cycloalkyl, allyl or benzyl and X has the meaning given, and this is subsequently converted by reaction with a metal alcoholate of the formula R 1 ″ ″ M n + , in which R 1 is alkyl, cycloalkyl, aryl or aralkyl and and M n + on
Alkali- oder Erdalkalimetallkation und n = 1 oder 2 bedeutet, und gegebenfalls weitere Behandlung mit einer schwachen Säure zu Enolethern der Formel Ib und/oder deren Enolen umgesetzt wird. Verbindungen der FormelAlkali or alkaline earth metal cation and n = 1 or 2 means, and if necessary further treatment with a weak acid is converted to enol ethers of the formula Ib and / or their enols. Compounds of the formula
Figure imgf000013_0001
worin X jeweils unabhängig voneinander F, Cl oder Br bedeutet und worin R2 Alkyl, Cycloalkyl, Allyl oder Benzyl ist.
Figure imgf000013_0001
wherein X each independently represents F, Cl or Br and wherein R 2 is alkyl, cycloalkyl, allyl or benzyl.
Verbindungen der FormelCompounds of the formula
Figure imgf000013_0002
sowie deren Enolen und E- und Z-Isomeren worin X jeweils unabhängig voneinander Fluor, Chlor oder Brom bedeutet, und worin R Alkyl, Cycloalkyl, Aryl oder Aralkyl ist, sowie worin R Alkyl, Cycloalkyl, Allyl oder Benzyl ist.
Figure imgf000013_0002
and their enols and E and Z isomers in which X is independently fluorine, chlorine or bromine, and in which R is alkyl, cycloalkyl, aryl or aralkyl, and in which R is alkyl, cycloalkyl, allyl or benzyl.
PCT/EP2004/011970 2003-10-24 2004-10-22 Method for the production of 6,6,6-trihalo-3,5-dioxohexanoic acid esters WO2005040087A1 (en)

Priority Applications (6)

Application Number Priority Date Filing Date Title
CA002541843A CA2541843A1 (en) 2003-10-24 2004-10-22 Method for the production of 6,6,6-trihalo-3,5-dioxohexanoic acid esters
EP04817266A EP1680391A1 (en) 2003-10-24 2004-10-22 Method for the production of 6,6,6-trihalo-3,5-dioxohexanoic acid esters
US10/577,070 US7351851B2 (en) 2003-10-24 2004-10-22 Method for the production of 6,6,6-trihalo-3,5-dioxohexanoic acid esters
JP2006536059A JP4638441B2 (en) 2003-10-24 2004-10-22 Method for producing 6,6,6-trihalo-3,5-dioxohexanoic acid ester
US11/416,212 US7348450B2 (en) 2003-10-24 2006-05-03 Method for the production of 6,6,6-trihalo-3,5-dioxohexanoic acid esters
US12/071,991 US7781601B2 (en) 2003-10-24 2008-02-28 Method for the production of 6,6,6-trihalo-3,5-dioxohexanoic acid esters

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP03024344 2003-10-24
EP03024344.8 2003-10-24

Related Child Applications (3)

Application Number Title Priority Date Filing Date
US10/577,070 A-371-Of-International US7351851B2 (en) 2003-10-24 2004-10-22 Method for the production of 6,6,6-trihalo-3,5-dioxohexanoic acid esters
US11/416,212 Continuation-In-Part US7348450B2 (en) 2003-10-24 2006-05-03 Method for the production of 6,6,6-trihalo-3,5-dioxohexanoic acid esters
US12/071,991 Division US7781601B2 (en) 2003-10-24 2008-02-28 Method for the production of 6,6,6-trihalo-3,5-dioxohexanoic acid esters

Publications (1)

Publication Number Publication Date
WO2005040087A1 true WO2005040087A1 (en) 2005-05-06

Family

ID=34486096

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2004/011970 WO2005040087A1 (en) 2003-10-24 2004-10-22 Method for the production of 6,6,6-trihalo-3,5-dioxohexanoic acid esters

Country Status (6)

Country Link
US (3) US7351851B2 (en)
EP (1) EP1680391A1 (en)
JP (1) JP4638441B2 (en)
CN (3) CN101693664A (en)
CA (1) CA2541843A1 (en)
WO (1) WO2005040087A1 (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2648805C (en) * 2008-01-09 2011-08-16 Sandvik Mining And Construction Downhole tool for rock drilling
WO2012061012A2 (en) * 2010-11-02 2012-05-10 The University Of North Carolina At Chapel Hill 4-amino-2h-pyran-2-one analogs as anticancer agents

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002002547A1 (en) * 2000-06-30 2002-01-10 Merck Frosst Canada & Co. Pyrones as inhibitors of cyclooxygenase-2

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0649039A (en) 1992-06-04 1994-02-22 Nippon Soda Co Ltd Pyrimidine derivative, herbicide and fungicide for agricultural and horticultural use
ZA938019B (en) 1992-11-13 1995-04-28 Upjohn Co Pyran-2-ones and 5,6-dihydropyran-2-ones useful for treating HIV and other retroviruses
JPH1087568A (en) * 1996-09-13 1998-04-07 Nippon Soda Co Ltd Production of optically active delta-hydroxy-betaketoester
DE19857302C2 (en) * 1998-12-14 2000-10-26 Forschungszentrum Juelich Gmbh Process for the enantioselective reduction of 3,5-dioxocarboxylic acids, their salts and esters
US6476235B2 (en) 2001-01-09 2002-11-05 Warner-Lambert Company Process for the synthesis of 5-(4-fluorophenyl)-1-[2-((2R,4R)-4-hydroxy-6-oxo-tetrahydro-pyran-2-yl)-ethyl]-2-isopropyl-4-phenyl-1H-pyrrole-3-carboxylic acid phenylamide

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002002547A1 (en) * 2000-06-30 2002-01-10 Merck Frosst Canada & Co. Pyrones as inhibitors of cyclooxygenase-2

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
G. SOLLADIE ET AL.: "Chiral Sulfoxides in Asymmetric Syntheis", TETRAHEDRON: ASYMMETRY., vol. 7, no. 8, 1996, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM., NL, pages 2371 - 2379, XP004048293 *
TETSURO SHIMO, KENICHI SOMEKAWA ET AL.: "Preparation of 3-(2H-Pyran-2-on-6-yl)indolizines and the Diels-Alder Reactions with Some Olefinic and Acetylenic Dienophiles", JOURNAL OF HETEROCYCLIC CHEMISTRY., vol. 28, 1991, USHETERO CORP., TAMPA, FL., pages 1831 - 1833, XP002313237 *
W. T. BRADY ET AL.: "The Synthesis of Pyranones Utilizing the (4+2) Cycloaddition of Ketenes and Siloxy Dienes", JOURNAL OF HETEROCYCLIC CHEMISTRY., vol. 20, 1983, USHETERO CORP., TAMPA, FL., pages 501 - 506, XP002313239 *

Also Published As

Publication number Publication date
CN1871202A (en) 2006-11-29
EP1680391A1 (en) 2006-07-19
JP4638441B2 (en) 2011-02-23
US20080161582A1 (en) 2008-07-03
US7351851B2 (en) 2008-04-01
US20070083061A1 (en) 2007-04-12
CN102030645A (en) 2011-04-27
US7781601B2 (en) 2010-08-24
JP2007509105A (en) 2007-04-12
US7348450B2 (en) 2008-03-25
CA2541843A1 (en) 2005-05-06
CN101693664A (en) 2010-04-14
US20060235240A1 (en) 2006-10-19

Similar Documents

Publication Publication Date Title
EP0219055B1 (en) Process for the manufacture of clausenamide
DE2608932C2 (en) Process for the preparation of 3-oxy-4H-pyran-4-one derivatives
WO2005040087A1 (en) Method for the production of 6,6,6-trihalo-3,5-dioxohexanoic acid esters
EP0095047B1 (en) Process for the preparation of 3-vinyl-substituted 2,2-dimethyl-cyclopropane-1-carboxylic acids or their esters, and intermediate products therefor
EP3301092A2 (en) Process for the production of spiroketal-substituted phenylacetylamino acid esters and spiroketal-substituted cyclic ketoenols
EP0112502B1 (en) Carboxylic esters and aldehydes of omega,omega-diacyloxy-2,6-dimethyl octatriene, process for their preparation and their use in the synthesis of terpene compounds
DE3338853C2 (en) Process for the preparation of 2-cyclopentenones
DE3338832C2 (en)
DE10019291C2 (en) 2-alkoxy-5-methoxypyrimidines or their tautomeric forms and processes for their preparation
EP0678515B1 (en) Process and intermediates for the production of 5-oxaspiro [2.4] heptan-6-one
EP0446925B1 (en) Process for the preparation of beta-resorcylic acid derivatives
DE2457555C3 (en) Process for the preparation of 1,2-disubstituted trans-olefins
DD289528A5 (en) PROCESS FOR PREPARING A [2,3-TRANE] TETRAHYDRO-2-PHENYL-5-HYDROXY-3-HYDROXYMETHYL FURANE
DE4012792A1 (en) METHOD FOR PRODUCING 1-ALKOXYHEXATRIA-2-CARBONIC ACID ESTERS
EP0206294B1 (en) Alkyl esters of 3-hydroxy-3-(2-methyl-5-pyridyl)-propionic acid
DE19832146B4 (en) Process for the preparation of 3-methylpyrazole or its salts
EP0182168A2 (en) Process for the preparation of esters of hydroxymethylene-alcoxyacetic acid
DE2543732A1 (en) DERIVATIVES OF 3ALPHA,5ALPHA-CYCLO-6BETA-ALKOXY-25-HYDROXYCHOLESTEROL AND 3ALPHA,5ALPHA-CYCLO-6BETA-ALKOXYCHOLEST-22T-EN-24,25-OXIDE, METHOD FOR PRODUCING THE SAME AND INTERMEDIATE PRODUCTS FOR HYDROXYLATED VITA MIN D LOW 2 AND D DEEP 3
DE10047111A1 (en) Process for the preparation of DELTA · 1 · pyrrolines
WO2006079608A2 (en) Method for producing 2-oxo-cycloalkane carboxylic acid ethyl esters and 2-oxo-cycloalkene carboxylic acid ethyl esters
EP1771434A2 (en) Method for the production of 3-amino-5-(hydroxymethyl)cyclopentane-1,2-diol derivatives
DE102006007895A1 (en) Preparing 2-(1-hydroxy alkyl)-cyclopent-2-enone compound, useful to prepare cyclopentanone compound, comprises reacting 2-cyclopentenone with aliphatic aldehyde compound in the presence of a bicarbonate solution and imidazole
DE2360409A1 (en) HEXAHYDRO-CYCLOPENTA SQUARE BRACKET ON SQUARE BRACKET FOR FURANDERIVATES AND THE PROCESS FOR THEIR MANUFACTURING
EP0906266A1 (en) Process for preparation of substituted cycloalkyl ketones
EP0725055A1 (en) Process for the preparation of 5-oxo-6-heptenoic acid alkyl esters as well as intermediates for their preparation

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 200480031436.1

Country of ref document: CN

AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): BW GH GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DPEN Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed from 20040101)
WWE Wipo information: entry into national phase

Ref document number: 2541843

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 2004817266

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 2006536059

Country of ref document: JP

WWE Wipo information: entry into national phase

Ref document number: 2288/DELNP/2006

Country of ref document: IN

WWE Wipo information: entry into national phase

Ref document number: 11416212

Country of ref document: US

WWE Wipo information: entry into national phase

Ref document number: 2007083061

Country of ref document: US

Ref document number: 10577070

Country of ref document: US

WWP Wipo information: published in national office

Ref document number: 2004817266

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 11416212

Country of ref document: US

WWP Wipo information: published in national office

Ref document number: 10577070

Country of ref document: US